What have we learned from mouse models for cystic fibrosis?

References

• Kuller JA, Baughman R, Biolsi C. Cystic fibrosis and the National Institutes of Health consensus statement: are obstetrician-gynecologists ready to comply? Obstet. Gynecol.93(4), 581–584 (1999).
   PubMed Web of Science ®Google Scholar
• Kerem B, Rommens JM, Buchanan JA et al. Identification of the cystic fibrosis gene: genetic analysis. Science245(4922), 1073–1080 (1989).
   PubMed Web of Science ®Google Scholar
• Riordan JR, Rommens JM, Kerem B et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science245(4922), 1066–1073 (1989).
   PubMed Web of Science ®Google Scholar
• Rommens JM, Iannuzzi MC, Kerem B et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science245(4922), 1059–1065 (1989).
   PubMed Web of Science ®Google Scholar
• Rowntree RK, Harris A. The phenotypic consequences of CFTR mutations. Ann. Hum. Genet.67(Pt 5), 471–485 (2003).
   PubMed Web of Science ®Google Scholar
• Cheng SH, Gregory RJ, Marshall J et al. Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell63(4), 827–834 (1990).
   PubMed Web of Science ®Google Scholar
• Dalemans W, Barbry P, Champigny G et al. Altered chloride ion channel kinetics associated with the ΔF508 cystic fibrosis mutation. Nature354(6354), 526–528 (1991).
   PubMed Web of Science ®Google Scholar
• Gregory RJ, Rich DP, Cheng SH et al. Maturation and function of cystic fibrosis transmembrane conductance regulator variants bearing mutations in putative nucleotide-binding domains 1 and 2. Mol. Cell. Biol.11(8), 3886–3893 (1991).
   PubMed Web of Science ®Google Scholar
• Lukacs GL, Mohamed A, Kartner N, Chang XB, Riordan JR, Grinstein S. Conformational maturation of CFTR but not its mutant counterpart (ΔF508) occurs in the endoplasmic reticulum and requires ATP. EMBO J.13(24), 6076–6086 (1994).
   PubMed Web of Science ®Google Scholar
• Pedemonte N, Lukacs GL, Du K et al. Small-molecule correctors of defective ΔF508-CFTR cellular processing identified by high-throughput screening. J. Clin. Invest.115(9), 2564–2571 (2005).
   PubMed Web of Science ®Google Scholar
• Sharma M, Benharouga M, Hu W, Lukacs GL. Conformational and temperature-sensitive stability defects of the ΔF508 cystic fibrosis transmembrane conductance regulator in post-endoplasmic reticulum compartments. J. Biol. Chem.276(12), 8942–8950 (2001).
   PubMed Web of Science ®Google Scholar
• Yang H, Shelat AA, Guy RK et al. Nanomolar affinity small molecule correctors of defective ΔF508-CFTR chloride channel gating. J. Biol. Chem.278(37), 35079–35085 (2003).
   PubMed Web of Science ®Google Scholar
• Guggino WB, Stanton BA. New insights into cystic fibrosis: molecular switches that regulate CFTR. Nat. Rev. Mol. Cell. Biol.7(6), 426–436 (2006).
   PubMed Web of Science ®Google Scholar
• Scholte BJ, Colledge WH, Wilke M, Jonge H. Cellular and animal models of cystic fibrosis, tools for drug discovery. Drug Discov. Today3(3), 251–259 (2006).
   Google Scholar
• Ellsworth RE, Jamison DC, Touchman JW et al. Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes. Proc. Natl Acad. Sci. USA97(3), 1172–1177 (2000).
   PubMed Web of Science ®Google Scholar
• Tata F, Stanier P, Wicking C et al. Cloning the mouse homolog of the human cystic fibrosis transmembrane conductance regulator gene. Genomics10(2), 301–307 (1991).
   PubMed Web of Science ®Google Scholar
• Thomas KR, Capecchi MR. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell51(3), 503–512 (1987).
   PubMed Web of Science ®Google Scholar
• Snouwaert JN, Brigman KK, Latour AM et al. An animal model for cystic fibrosis made by gene targeting. Science257(5073), 1083–1088 (1992).
   PubMed Web of Science ®Google Scholar
• Dorin JR, Dickinson P, Alton EW et al. Cystic fibrosis in the mouse by targeted insertional mutagenesis. Nature359(6392), 211–215 (1992).
   PubMed Web of Science ®Google Scholar
• Hasty P, O’Neal WK, Liu KQ et al. Severe phenotype in mice with termination mutation in exon 2 of cystic fibrosis gene. Somat. Cell Mol. Genet.21(3), 177–187 (1995).
   PubMedGoogle Scholar
• O’Neal WK, Hasty P, McCray PB Jr et al. A severe phenotype in mice with a duplication of exon 3 in the cystic fibrosis locus. Hum. Mol. Genet.2(10), 1561–1569 (1993).
   PubMed Web of Science ®Google Scholar
• Ratcliff R, Evans MJ, Cuthbert AW et al. Production of a severe cystic fibrosis mutation in mice by gene targeting. Nat. Genet.4(1), 35–41 (1993).
   PubMed Web of Science ®Google Scholar
• Rozmahel R, Wilschanski M, Matin A et al. Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor. Nat. Genet.12(3), 280–287 (1996).
   PubMed Web of Science ®Google Scholar
• Colledge WH, Abella BS, Southern KW et al. Generation and characterization of a ΔF508 cystic fibrosis mouse model. Nat. Genet.10(4), 445–452 (1995).
   PubMed Web of Science ®Google Scholar
• van Doorninck JH, French PJ, Verbeek E et al. A mouse model for the cystic fibrosis ΔF508 mutation. EMBO J.14(18), 4403–4411 (1995).
   PubMed Web of Science ®Google Scholar
• Zeiher BG, Eichwald E, Zabner J et al. A mouse model for the ΔF508 allele of cystic fibrosis. J. Clin. Invest.96(4), 2051–2064 (1995).
   PubMed Web of Science ®Google Scholar
• French PJ, van Doorninck JH, Peters RH et al. A ΔF508 mutation in mouse cystic fibrosis transmembrane conductance regulator results in a temperature-sensitive processing defect in vivo. J. Clin. Invest.98(6), 1304–1312 (1996).
   PubMed Web of Science ®Google Scholar
• Delaney SJ, Alton EW, Smith SN et al. Cystic fibrosis mice carrying the missense mutation G551D replicate human genotype-phenotype correlations. EMBO J.15(5), 955–963 (1996).
   PubMed Web of Science ®Google Scholar
• Logan J, Hiestand D, Daram P et al. Cystic fibrosis transmembrane conductance regulator mutations that disrupt nucleotide binding. J. Clin. Invest.94(1), 228–236 (1994).
   PubMed Web of Science ®Google Scholar
• Smit LS, Strong TV, Wilkinson DJ et al. Missense mutation (G480C) in the CFTR gene associated with protein mislocalization but normal chloride channel activity. Hum. Mol. Genet.4(2), 269–273 (1995).
   PubMed Web of Science ®Google Scholar
• Dickinson P, Kimber WL, Kilanowski FM et al. Enhancing the efficiency of introducing precise mutations into the mouse genome by hit and run gene targeting. Transgenic Res.9(1), 55–66 (2000).
   PubMed Web of Science ®Google Scholar
• Scholte BJ, Davidson DJ, Wilke M, De Jonge HR. Animal models of cystic fibrosis. J. Cyst. Fibros.3(Suppl. 2), 183–190 (2004).
   PubMedGoogle Scholar
• Lindert J, Perlman CE, Parthasarathi K, Bhattacharya J. Chloride-dependent secretion of alveolar wall liquid determined by optical-sectioning microscopy. Am. J. Respir. Cell. Mol. Biol.36(6), 688–896 (2007).
   PubMed Web of Science ®Google Scholar
• Freedman SD, Weinstein D, Blanco PG et al. Characterization of LPS-induced lung inflammation in cftr-/- mice and the effect of docosahexaenoic acid. J. Appl. Physiol.92(5), 2169–2176 (2002).
   PubMed Web of Science ®Google Scholar
• van Heeckeren AM, Schluchter MD, Xue W, Davis PB. Response to acute lung infection with mucoid Pseudomonas aeruginosa in cystic fibrosis mice. Am. J. Respir. Crit. Care Med.173(3), 288–296 (2006).
   PubMed Web of Science ®Google Scholar
• Gosselin D, Stevenson MM, Cowley EA et al. Impaired ability of Cftr knockout mice to control lung infection with Pseudomonas aeruginosa. Am. J. Respir. Crit. Care Med.157(4 Pt 1), 1253–1262 (1998).
   PubMed Web of Science ®Google Scholar
• McMorran BJ, Palmer JS, Lunn DP et al. G551D CF mice display an abnormal host response and have impaired clearance of Pseudomonas lung disease. Am. J. Physiol. Lung Cell. Mol. Physiol.281(3), L740–L747 (2001).
   PubMed Web of Science ®Google Scholar
• Legssyer R, Huaux F, Lebacq J et al. Azithromycin reduces spontaneous and induced inflammation in ΔF508 cystic fibrosis mice. Respir. Res.7, 134 (2006).
   PubMed Web of Science ®Google Scholar
• Kent G, Iles R, Bear CE et al. Lung disease in mice with cystic fibrosis. J. Clin. Invest.100(12), 3060–3069 (1997).
   PubMed Web of Science ®Google Scholar
• Durie PR, Kent G, Phillips MJ, Ackerley CA. Characteristic multiorgan pathology of cystic fibrosis in a long-living cystic fibrosis transmembrane regulator knockout murine model. Am. J. Pathol.164(4), 1481–1493 (2004).
   PubMed Web of Science ®Google Scholar
• Bronsveld I, Mekus F, Bijman J et al. Residual chloride secretion in intestinal tissue of ΔF508 homozygous twins and siblings with cystic fibrosis. The European CF Twin and Sibling Study Consortium. Gastroenterology119(1), 32–40 (2000).
   PubMed Web of Science ®Google Scholar
• Mekus F, Laabs U, Veeze H, Tummler B. Genes in the vicinity of CFTR modulate the cystic fibrosis phenotype in highly concordant or discordant F508del homozygous sib pairs. Hum. Genet.112(1), 1–11 (2003).
   PubMed Web of Science ®Google Scholar
• Boyle MP. Strategies for identifying modifier genes in cystic fibrosis. Proc. Am. Thorac. Soc.4(1), 52–57 (2007).
   PubMedGoogle Scholar
• Knowles MR. Gene modifiers of lung disease. Curr. Opin. Pulm. Med.12(6), 416–421 (2006).
   PubMed Web of Science ®Google Scholar
• Stanke F, Tummler B, Becker T. Genetic modifiers in cystic fibrosis. N. Engl. J. Med.354(1), 88–90; author reply 88–90 (2006).
   PubMed Web of Science ®Google Scholar
• Allan JD, Mason A, Moss AD. Nutritional supplementation in treatment of cystic fibrosis of the pancreas. Am. J. Dis. Child.126(1), 22–26 (1973).
   PubMedGoogle Scholar
• Berry HK, Kellogg FW, Hunt MM, Ingberg RL, Richter L, Gutjahr C. Dietary supplement and nutrition in children with cystic fibrosis. Am. J. Dis. Child.129(2), 165–171 (1975).
   PubMedGoogle Scholar
• Shepherd R, Cooksley WG, Cooke WD. Improved growth and clinical, nutritional, and respiratory changes in response to nutritional therapy in cystic fibrosis. J. Pediatr.97(3), 351–357 (1980).
   PubMed Web of Science ®Google Scholar
• Tirouvanziam R. Neutrophilic inflammation as a major determinant in the progression of cystic fibrosis. Drug News Perspect.19(10), 609–614 (2006).
   PubMedGoogle Scholar
• Dinwiddie R. Pathogenesis of lung disease in cystic fibrosis. Respiration67(1), 3–8 (2000).
   PubMed Web of Science ®Google Scholar
• Konstan MW, Berger M. Current understanding of the inflammatory process in cystic fibrosis: onset and etiology. Pediatr. Pulmonol.24(2), 137–142; discussion 159–161 (1997).
   PubMed Web of Science ®Google Scholar
• Hajj R, Lesimple P, Nawrocki-Raby B, Birembaut P, Puchelle E, Coraux C. Human airway surface epithelial regeneration is delayed and abnormal in cystic fibrosis. J. Pathol.211(3), 340–350 (2007).
   PubMed Web of Science ®Google Scholar
• Tirkos S, Newbigging S, Nguyen V et al. Expression of S100A8 correlates with inflammatory lung disease in congenic mice deficient of the cystic fibrosis transmembrane conductance regulator. Respir. Res.7, 51 (2006).
   PubMedGoogle Scholar
• Mall M, Grubb BR, Harkema JR, O’Neal WK, Boucher RC. Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice. Nat. Med.10(5), 487–493 (2004).
   PubMed Web of Science ®Google Scholar
• Knowles MR, Boucher RC. Mucus clearance as a primary innate defense mechanism for mammalian airways. J. Clin. Invest.109(5), 571–577 (2002).
   PubMed Web of Science ®Google Scholar
• Guggino WB, Banks-Schlegel SP. Macromolecular interactions and ion transport in cystic fibrosis. Am. J. Respir. Crit. Care Med.170(7), 815–820 (2004).
   PubMed Web of Science ®Google Scholar
• Roomans GM. Pharmacological approaches to correcting the ion transport defect in cystic fibrosis. Am. J. Respir. Med.2(5), 413–431 (2003).
   PubMedGoogle Scholar
• Egan ME, Pearson M, Weiner SA et al. Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science304(5670), 600–602 (2004).
   PubMed Web of Science ®Google Scholar
• Song Y, Sonawane ND, Salinas D et al. Evidence against the rescue of defective ΔF508-CFTR cellular processing by curcumin in cell culture and mouse models. J. Biol. Chem.279(39), 40629–40633 (2004).
   PubMed Web of Science ®Google Scholar
• Berger AL, Randak CO, Ostedgaard LS, Karp PH, Vermeer DW, Welsh MJ. Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl-channel activity. J. Biol. Chem.280(7), 5221–5226 (2005).
   PubMed Web of Science ®Google Scholar
• Lipecka J, Norez C, Bensalem N et al. Rescue of ΔF508-CFTR (cystic fibrosis transmembrane conductance regulator) by curcumin: involvement of the keratin 18 network. J. Pharmacol. Exp. Ther.317(2), 500–505 (2006).
   PubMed Web of Science ®Google Scholar
• Wang W, Li G, Clancy JP, Kirk KL. Activating cystic fibrosis transmembrane conductance regulator channels with pore blocker analogs. J. Biol. Chem.280(25), 23622–23630 (2005).
   PubMed Web of Science ®Google Scholar
• Du M, Jones JR, Lanier J et al. Aminoglycoside suppression of a premature stop mutation in a Cftr-/- mouse carrying a human CFTR-G542X transgene. J. Mol. Med.80(9), 595–604 (2002).
   PubMed Web of Science ®Google Scholar
• Du M, Keeling KM, Fan L et al. Clinical doses of amikacin provide more effective suppression of the human CFTR-G542X stop mutation than gentamicin in a transgenic CF mouse model. J. Mol. Med.84(7), 573–582 (2006).
   PubMed Web of Science ®Google Scholar
• Wilschanski M, Yahav Y, Yaacov Y et al. Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations. N. Engl. J. Med.349(15), 1433–1441 (2003).
   PubMed Web of Science ®Google Scholar
• Walker NM, Simpson JE, Levitt RC, Boyle KT, Clarke LL. Talniflumate increases survival in a cystic fibrosis mouse model of distal intestinal obstructive syndrome. J. Pharmacol. Exp. Ther.317(1), 275–283 (2006).
   PubMed Web of Science ®Google Scholar
• Knight D. Talniflumate (Genaera). Curr. Opin. Investig. Drugs5(5), 557–562 (2004).
   PubMedGoogle Scholar
• Haston CK, Corey M, Tsui LC. Mapping of genetic factors influencing the weight of cystic fibrosis knockout mice. Mamm. Genome13(11), 614–618 (2002).
   PubMed Web of Science ®Google Scholar
• Haston CK, McKerlie C, Newbigging S, Corey M, Rozmahel R, Tsui LC. Detection of modifier loci influencing the lung phenotype of cystic fibrosis knockout mice. Mamm. Genome13(11), 605–613 (2002).
   PubMed Web of Science ®Google Scholar
• Bronsveld I, Mekus F, Bijman J et al. Chloride conductance and genetic background modulate the cystic fibrosis phenotype of ΔF508 homozygous twins and siblings. J. Clin. Invest.108(11), 1705–1715 (2001).
   PubMed Web of Science ®Google Scholar
• Drumm ML, Konstan MW, Schluchter MD et al. Genetic modifiers of lung disease in cystic fibrosis. N. Engl. J. Med.353(14), 1443–1453 (2005).
   PubMed Web of Science ®Google Scholar
• Chmiel JF, Konstan MW, Knesebeck JE et al. IL-10 attenuates excessive inflammation in chronic Pseudomonas infection in mice. Am. J. Respir. Crit. Care Med.160(6), 2040–2047 (1999).
   PubMed Web of Science ®Google Scholar
• Lee JY, Elmer HL, Ross KR, Kelley TJ. Isoprenoid-mediated control of SMAD3 expression in a cultured model of cystic fibrosis epithelial cells. Am. J. Respir. Cell Mol. Biol.31(2), 234–240 (2004).
   PubMed Web of Science ®Google Scholar
• Meng QH, Springall DR, Bishop AE et al. Lack of inducible nitric oxide synthase in bronchial epithelium: a possible mechanism of susceptibility to infection in cystic fibrosis. J. Pathol.184(3), 323–331 (1998).
   PubMed Web of Science ®Google Scholar
• Kelley TJ, Drumm ML. Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells. J. Clin. Invest.102(6), 1200–1207 (1998).
   PubMed Web of Science ®Google Scholar
• Ferrari S, Griesenbach U, Geddes DM, Alton E. Immunological hurdles to lung gene therapy. Clin. Exp. Immunol.132(1), 1–8 (2003).
   PubMed Web of Science ®Google Scholar
• Rosenecker J, Huth S, Rudolph C. Gene therapy for cystic fibrosis lung disease: current status and future perspectives. Curr. Opin. Mol. Ther.8(5), 439–445 (2006).
   PubMed Web of Science ®Google Scholar
• Griesenbach U, Geddes DM, Alton EW. Gene therapy progress and prospects: cystic fibrosis. Gene Ther.13(14), 1061–1067 (2006).
   PubMed Web of Science ®Google Scholar
• Ziady AG, Davis PB. Current prospects for gene therapy of cystic fibrosis. Curr. Opin. Pharmacol.6(5), 515–521 (2006).
   PubMed Web of Science ®Google Scholar
• Herzog EL, Chai L, Krause DS. Plasticity of marrow-derived stem cells. Blood102(10), 3483–3493 (2003).
   PubMed Web of Science ®Google Scholar
• Loi R, Beckett T, Goncz KK, Suratt BT, Weiss DJ. Limited restoration of cystic fibrosis lung epithelium in vivo with adult bone marrow-derived cells. Am. J. Respir. Crit. Care Med.173(2), 171–179 (2006).
   PubMed Web of Science ®Google Scholar
• Bruscia EM, Price JE, Cheng EC et al. Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation. Proc. Natl Acad. Sci. USA103(8), 2965–2970 (2006).
   PubMed Web of Science ®Google Scholar
• Kim CF, Jackson EL, Kirsch DG et al. Mouse models of human non-small-cell lung cancer: raising the bar. Cold Spring Harb. Symp. Quant. Biol.70, 241–250 (2005).
   PubMedGoogle Scholar
• Penque D. Proteomic biomarker discovery for the monogenic disease cystic fibrosis. Expert Rev. Proteomics4(2), 199–209 (2007).
   PubMed Web of Science ®Google Scholar
• Brouillard F, Bensalem N, Hinzpeter A et al. Blue native/SDS-PAGE analysis reveals reduced expression of the mClCA3 protein in cystic fibrosis knock-out mice. Mol. Cell Proteomics4(11), 1762–1775 (2005).
   PubMed Web of Science ®Google Scholar
• Sloane AJ, Lindner RA, Prasad SS et al. Proteomic analysis of sputum from adults and children with cystic fibrosis and from control subjects. Am. J. Respir. Crit. Care Med.172(11), 1416–1426 (2005).
   PubMed Web of Science ®Google Scholar
• Roxo-Rosa M, da Costa G, Luider TM et al. Proteomic analysis of nasal cells from cystic fibrosis patients and non-cystic fibrosis control individuals: search for novel biomarkers of cystic fibrosis lung disease. Proteomics6(7), 2314–2325 (2006).
   PubMed Web of Science ®Google Scholar
• Yang L, Reece J, Gabriel SE, Shears SB. Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis. J. Cell Sci.119(Pt 7), 1320–1328 (2006).
   PubMed Web of Science ®Google Scholar
• Liang L, Zsembery A, Schwiebert EM. RNA interference targeted to multiple P2X receptor subtypes attenuates zinc-induced calcium entry. Am. J. Physiol. Cell Physiol.289(2), C388–C396 (2005).
   PubMed Web of Science ®Google Scholar
• Mall M, Bleich M, Greger R, Schreiber R, Kunzelmann K. The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways. J. Clin. Invest.102(1), 15–21 (1998).
   PubMed Web of Science ®Google Scholar
• Matsui H, Grubb BR, Tarran R et al. Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell95(7), 1005–1015 (1998).
   PubMed Web of Science ®Google Scholar
• Boucher RC. New concepts of the pathogenesis of cystic fibrosis lung disease. Eur. Respir. J.23(1), 146–158 (2004).
   PubMed Web of Science ®Google Scholar
• Sheridan MB, Fong P, Groman JD et al. Mutations in the β-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome. Hum. Mol. Genet.14(22), 3493–3498 (2005).
   PubMed Web of Science ®Google Scholar
• Boucher RC. Evidence for airway surface dehydration as the initiating event in CF airway disease. J. Intern. Med.261(1), 5–16 (2007).
   PubMed Web of Science ®Google Scholar
• Boucher RC. Airway surface dehydration in cystic fibrosis: pathogenesis and therapy. Ann. Rev. Med.58, 157–170 (2007).
   PubMed Web of Science ®Google Scholar
• Joo NS, Irokawa T, Robbins RC, Wine JJ. Hyposecretion, not hyperabsorption, is the basic defect of cystic fibrosis airway glands. J. Biol. Chem.281(11), 7392–7398 (2006).
   PubMed Web of Science ®Google Scholar
• Wine JJ. Acid in the airways. Focus on “Hyperacidity of secreted fluid from submucosal glands in early cystic fibrosis”. Am. J. Physiol. Cell Physiol.290(3), C669–C671 (2006).
   PubMed Web of Science ®Google Scholar
• Wine JJ. Parasympathetic control of airway submucosal glands: central reflexes and the airway intrinsic nervous system. Auton. Neurosci.133(1), 35–54 (2007).
   PubMed Web of Science ®Google Scholar
• Wu JV, Krouse ME, Wine JJ. Acinar origin of CFTR-dependent airway submucosal gland fluid secretion. Am. J. Physiol. Cell Physiol.292(1), L304–L311 (2007).
   PubMed Web of Science ®Google Scholar
• Ianowski JP, Choi JY, Wine JJ, Hanrahan JW. Mucus secretion by single tracheal submucosal glands from normal and cystic fibrosis transmembrane conductance regulator knockout mice. J. Physiol.580(Pt 1), 301–314 (2007).
   PubMed Web of Science ®Google Scholar
• Grubb BR, Boucher RC. Pathophysiology of gene-targeted mouse models for cystic fibrosis. Physiol. Rev.79(1 Suppl.), S193–S214 (1999).
   PubMedGoogle Scholar
• Heeckeren A, Walenga R, Konstan MW, Bonfield T, Davis PB, Ferkol T. Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa. J. Clin. Invest.100(11), 2810–2815 (1997).
   PubMed Web of Science ®Google Scholar
• van Heeckeren AM, Schluchter MD. Murine models of chronic Pseudomonas aeruginosa lung infection. Lab. Anim.36(3), 291–312 (2002).
   PubMed Web of Science ®Google Scholar
• van Heeckeren AM, Schluchter MD, Drumm ML, Davis PB. Role of Cftr genotype in the response to chronic Pseudomonas aeruginosa lung infection in mice. Am. J. Physiol. Lung Cell Mol. Physiol.287(5), L944–L952 (2004).
   PubMed Web of Science ®Google Scholar
• Wieland CW, Siegmund B, Senaldi G, Vasil ML, Dinarello CA, Fantuzzi G. Pulmonary inflammation induced by Pseudomonas aeruginosa lipopolysaccharide, phospholipase C, and exotoxin A: role of interferon regulatory factor 1. Infect. Immun.70(3), 1352–1358 (2002).
   PubMed Web of Science ®Google Scholar
• Davidson DJ, Dorin JR, McLachlan G et al. Lung disease in the cystic fibrosis mouse exposed to bacterial pathogens. Nat. Genet.9(4), 351–357 (1995).
   PubMed Web of Science ®Google Scholar
• Davidson DJ, Webb S, Teague P, Govan JR, Dorin JR. Lung pathology in response to repeated exposure to Staphylococcus aureus in congenic residual function cystic fibrosis mice does not increase in response to decreased CFTR levels or increased bacterial load. Pathobiology71(3), 152–158 (2004).
   PubMed Web of Science ®Google Scholar
• Schroeder TH, Lee MM, Yacono PW et al. CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS from the outer membrane into epithelial cells and activates NF-κB translocation. Proc. Natl Acad. Sci. USA99(10), 6907–6912 (2002).
   PubMed Web of Science ®Google Scholar
• Leal T, Reychler G, Mailleux P, Gigi J, Godding V, Lebecque P. A specific database for providing local and national level of integration of clinical data in cystic fibrosis. J. Cyst. Fibros.6(3), 187–193 (2006).
   PubMed Web of Science ®Google Scholar
• White NM, Jiang D, Burgess JD, Bederman IR, Previs SF, Kelley TJ. Altered cholesterol homeostasis in cultured and in vivo models of cystic fibrosis. Am. J. Physiol. Lung Cell Mol. Physiol.292(2), L476–L486 (2007).
   PubMed Web of Science ®Google Scholar
• Colledge WH, Ratcliff R, Foster D, Williamson R, Evans MJ. Cystic fibrosis mouse with intestinal obstruction. Lancet340(8820), 680 (1992).
   PubMed Web of Science ®Google Scholar
• Wilschanski MA, Rozmahel R, Beharry S et al. In vivo measurements of ion transport in long-living CF mice. Biochem. Biophys. Res. Commun.219(3), 753–759 (1996).
   PubMed Web of Science ®Google Scholar
• Reynaert I, Van Der Schueren B, Degeest G et al. Morphological changes in the vas deferens and expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in control, deltaF508 and knock-out CFTR mice during postnatal life. Mol. Reprod. Dev.55(2), 125–135 (2000).
   PubMedGoogle Scholar
• Dickinson P, Kimber WL, Kilanowski FM et al. Enhancing the efficiency of introducing precise mutations into the mouse genome by hit and run gene targeting. Transgenic Res.9(1), 55–66 (2000).
   PubMed Web of Science ®Google Scholar
• Dickinson P, Smith SN, Webb S et al. The severe G480C cystic fibrosis mutation, when replicated in the mouse, demonstrates mistrafficking, normal survival and organ-specific bioelectrics. Hum. Mol. Genet.11(3), 243–251 (2002).
   PubMed Web of Science ®Google Scholar
• Davidson DJ, Dorin JR. The CF mouse: an important tool for studying cystic fibrosis. Expert Rev. Mol. Med.17(10), S29–S37 (2001).
   Google Scholar